However, there are a few retrospective population based studies that suggest benefit to local therapy in the setting of metastatic disease. Culp et al. (EU 2014) found that men treated with XRT or RP in setting of de novo mPCa had improved cancer-specific survival in the SEER database.
Based on the strength of this and other retrospective series, Dr. Kim completed an initial phase 1 trial (NCT02458716) looking at the safety and feasibility of CRP in setting of de novo mPCa. They included men with cN1 or cM1a/b disease, resectable disease (surgeon discretion), and ECOG 0-1. Primary outcomes was 90 day peri-operative complication rate.
They consented 36 patients, of which 32 completed surgery (2 US and 2 Korean institutions). All were robotic prostatectomies. Mean OR time was longer than localized disease: 262 minutes. There were 2 major complications: ATN requiring hemodialysis (1 patient) and 1 death at 5 days (presumed PE).
In terms of PSA response, 19 patients actually had PSA nadir <0.2 (67.9%), while 8 had a decrease but did not reach 0.2. One patient actually had rapid PSA rise.
Early continence was only 50%, but interestingly, IPSS scores improved after surgery. Likely attributable to fact that 2 patients came in with SP tube due to obstruction. So, even though continence isn’t great, surgery may help avoid local symptoms in these patients.
As such, based on this, they concluded CRP was feasible (but difficult). Oncologic outcomes promising.
This led to development of SIMCAP trial. Hypothesis: CRP will render systemic therapy more effective and enhance QOL in men with mPCa.
- This is a phase 2 3 study. Starts as phase II (primary endpoint is failure-free survival at 2 years) and switches to phase III (primary endpoint now overall survival) is original endpoint met.
- Planned initial enrollment 190 for first part, then additional 670 patients randomized
1. 1:1 randomization to BST + CRP vs. BST alone (discretion of medical oncologist)
2. Phase III only if 30% improvement in 2-year failure-free survival for initial 190 patients
Failure defined as: biochemical recurrence, clinical recurrence, death from PCa
3. Only cM1a/b patients – no cN1M0 patients
4. No limits on number of metastatic sites
5. Genomics and QOL assessment will be done as part of the trial
The study schema is as follows:
Currently, there is planned 27 institutions from 5 countries! At this time, 14 patients have been consented and randomized at Rutgers. All sites should be open by June 2019.
Initial results of phase II study ~2020.
He did note that this is one of three studies in this space, each slightly different in outcomes and inclusion criteria. Yet, all three will help address this question.
Presented by: Isaac Kim, United States
1. Dall’Era et al. Cancer 2014.
2. Culp et al. EU 2014.
Written By: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University Twitter: @tchandra_uromd, @TjuUrology at the 38th Congress of the Society of International Urology - October 4- 7, 2018 - Seoul, South Korea